Key result
Mitochondrial ADP/ATP carrier autoantibodies alter myocyte calcium gating and prolong action potentials in cardiomyopathy.
Why the study?
Autoantibodies to the mitochondrial ADP/ATP carrier in myocarditis and dilated cardiomyopathy crossreact with the cardiac myocyte plasma membrane, raising the possibility that they disturb the calcium channel and contribute to electrophysiological and contractile abnormalities.
Answers are grounded in this paper and cite their sources.
Suggests autoimmune contribution to electrophysiologic changes in myocarditis and DCM; leaves open diagnostic or therapeutic relevance pending validation.
We recently described autoantibodies to the ADP/ATP carrier of the inner mitochondrial membrane as an organ specific autoantigen found in high frequencies in sera of patients with myocarditis and dilated cardiomyopathy. These antibodies not only showed an intracellular binding at the mitochondrial membrane, but also crossreact with antigenic determinants at the cardiac myocyte plasma membrane. They therefore may account, at least in part, for the so-called sarcolemmal-bound IgG of heart-reactive autoantibodies found to be associated with these diseases. Heart muscle diseases are associated with electrocardiographic abnormalities such as complex ventricular arrhythmias and disturbed ventricular function. Our data indicate that abnormalities in current spread and impaired heart contractility might also be caused by an antibody mediated disturbance of calcium channel gating leading to prolongation of the action potential and potentiation of tension. The enhanced calcium permeability of the cell may moreover cause calcium overload and cell death. The calcium channel complex plays a central role in cardiac contractility. Disturbing calcium channel gating by antibodies might therefore contribute to the pathogenesis of these diseases.
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Kühl et al. (1991) studied Myocarditis and dilated cardiomyopathy. Autoantibodies to the ADP/ATP carrier of the inner mitochondrial membrane was evaluated on Calcium channel gating disturbance, action potential prolongation, and tension potentiation. Autoantibodies to the mitochondrial ADP/ATP carrier crossreact with the myocyte plasma membrane, disturbing calcium channel gating and prolonging action potentials in myocarditis and DCM.
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